title: A phase I, dose-escalation study of cyclical weekly oral temozolomide and weekly PEG-interferon alpha-2b in patients with refractory or advanced solid tumours.
abstract: BACKGROUND
  Temozolomide (TMZ) is an oral alkylating agent used in the treatment of central nervous system neoplasms and metastatic melanoma. Preclinical and clinical data suggested that combining TMZ with interferon alpha-2b (IFN-alpha-2b) may result in increased anti-tumour efficacy.
  
  
  METHODS
  This was a phase I, dose-escalation study to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of cyclical oral TMZ (days 1-7 and 15-21) in combination with pegylated IFN-alpha-2b (PEG-IFN-alpha-2b) in patients with advanced solid tumours.
  
  
  RESULTS
  We treated 19 patients (10 female and nine male), median age 58 years (range: 41-79 years). Ten patients tolerated TMZ at 100 mg/m² on days 1-7 and 15-21 plus PEG-IFN-alpha-2b at 1.5 mcg/kg/week on 28-day cycles which was the MTD of the combination. The pharmacokinetic parameters of PEG-IFN-alpha-2b were not altered by TMZ, at the MTD.
  
  
  CONCLUSIONS
  The MTD of cyclical oral TMZ was 100 mg/m² on days 1-7 and 15-21 when combined with weekly subcutaneous PEG-IFNα-2b at 1.5 mcg/kg/week on 28 days cycles. The PK of PEG-IFN-alpha-2b appeared consistent with those when it is used as monotherapy.
authors.forename: Shodeinde A
authors.initials: SA
authors.lastname: Coker
authors.forename: Uday B
authors.initials: UB
authors.lastname: Dandamudi
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Beelen
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Crosby
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.forename: Michael
authors.initials: M
authors.lastname: Obrocea
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D003606:Dacarbazine; C417083:peginterferon alfa-2b; D000077204:Temozolomide
keywords: PEG-IFN combination therapy; Phase I,; Temozolomide,